Bim mediates the elimination of functionally unfit Th1 responders from the memory pool.

Bim mediates the elimination of functionally unfit Th1 responders from the memory pool.
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DOI:
10.1371/journal.pone.0067363
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Williams MA
Williams MA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Jay DC;Mitchell DM;Williams MA

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Selective clonal deletion in the CD4+ T cell compartment during the transition from effector to memory is accompanied by enhanced expression of the pro-apoptotic Bcl-2 family member Bim. Here, we show that Bim deficiency enables the survival of poorly functional Th1 responders that are normally eliminated during contraction. However, rescued bim −/− CD4+ “memory” T cells continued to demonstrate deficient effector functions, poor sensitivity to antigen and an inability to respond to secondary challenge. Our results demonstrate that Bim activity plays a key role in shaping the CD4+ memory T cell repertoire, ensuring the emergence of highly functional CD4+ memory T cells and the elimination of Th1 effector cells with sub-optimal function. We propose that Bim is a key mediator of T cell death in the absence of appropriate TCR-driven activation and differentiation.
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